The overall goal of this application is to investigate the potential role of saliva and/or individual salivary constituents in modulating the in vitro infectivity of the human immunodeficiency virus (HIV). The studies proposed will be designed to verify and enlarge the initial observations of Fultz and Fox at al. If these initial observations are upheld, further experimentation will be directed towards identifying the salivary constituent(s) which modulate in vitro infectivity of HIV. These data will then be utilized to examine the mechanism(s) (e.g. surface mediated events and/or intracellular processes) whereby saliva exerts its effect on HIV/target cell interactions. To study HIV inhibitory factors in human saliva, we have established a team of biochemists with expertise in purification of salivary components, virologists with expertise in the biological mechanisms of HIV infectivity, and cell biologists with expertise in ultrastructure. Multiple assays are available which can examine the effects of saliva and individual salivary molecules on HIV-target cell interactions. We will be able to assess if the interaction of salivary secretions with virus affects binding with the target cell affects virus binding to the target cell surface. Our preliminary studies with another virus (e.g. HSV-I) suggest that interaction of target cells (e.g. fibroblasts) with mucin-containing fractions from HSMSL affects subsequent binding by virus. Incubation of HSV-I with HSMSL inhibits interaction with fibroblasts. This latter effect may be mediated by phosphorylated salivary cystatins. In addition, we have carried out preliminary experiments to test the effect of HSMSL and HPS in a quantitative transactivation-fusion assay involving viral gp120 and cellular CD4. Our initial results suggest that both salivary secretions can inhibit cell fusion with the effect of HSMSL > HPS. Finally, the use of electron microscopic techniques to visualize in vitro non-infective HIV- like viral particles in the proposed studies is also presented in our preliminary data. Collectively, these preliminary data support our capacity to carry out the proposed project and highlights the scientific capability of the research team. It is anticipated that the proposed studies will provide basic information regarding the anti-viral properties of saliva as well as the potential transmissibility of HIV by oral secretions. Furthermore, this information may furnish new insights towards developing new treatment and/or prevention modalities for oral as well as disseminated viral infections. Such knowledge could be invaluable for clinicians (both dentists and physicians), the scientific community at large, and the general public.